This application is for a new grant to study the mechanism of somatic hypermutation of immunoglobulin (Ig) genes. Our previous work has shown that this process depends on initiation of transcription. The new aims are directed at determining how transcription relates to the somatic mutation process, what the role is of the primary sequence which is the target for mutation and what the cis-acting regulatory elements consist of. Finally, we plan to clone and identify the gene(s) that encode a postulated mutator factor. These studies are important to understand the creation of the lg repertoire with the potential of reacting against any foreign antigen, including tumor antigens. Also, somatic hypermutation has been implicated in autoimmunities. Finally, certain malignant lymphoid tumors arise during the lg gene somatic mutation process and understanding its mechanism will shed light on the tumorigenesis and, hopefully, its prevention.